p53-mediated apoptosis and genomic instability diseases

Mutations in several DExH-containing DNA helicases, including XPD, XPB, WRN , and BLM, are associated with rare familial cancer syndromes characterized by genomic instability and cancer susceptibility. Known cellular activitie s of these helicases include DNA replication, repair, recombination, and/or transcription. The p53 tumor suppressor is a regulator of cellular respons es to stress, and is biochemically involved in the induction of cell-cycle arrest, apoptosis and DNA repair, all of which contribute to maintenance of genomic integrity. Physical and functional interactions of p53 with DExH-c ontaining DNA helicases have been described, We propose that such interacti ons could be compromised in inherited disorders and contribute to their can cer susceptibility. In particular, the role of DNA helicases in p53-mediate d apoptotic pathways is reviewed.